Sodium Hydroxide → 4-[3-(4-Carboxy-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic Acid Tert-butyl Ester

HRID 220841Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([O:26]CC)=[O:25])=[CH:20][C:19]=2[F:29])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=[O:25])=[CH:20][C:19]=2[F:29])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 4-[3-(4-ethoxycarbonyl-2-fluoro-phenoxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester from Example E39.1 (1.7 g, 4.1 mmol) in dioxan (25 ml) was treated with 2N NaOH (3 ml) and the mixture stirred at 50° C. for 18 h. A further aliquot of 2N NaOH was added (2 ml), and stirring continued at 50° C. for 3 h. Solvents were removed in vacuo and azeotroped with toluene. The residue was purified by flash chromatography on silica gel (eluant; 1% acetic acid:9% methanol:90% chloroform) to yield the title compound (1.45 g, 92%).

Workup

stirringstirring
waitcontinued at 50° C. for 3 h
customSolvents were removed in vacuo
customazeotroped with toluene
customThe residue was purified by flash chromatography on silica gel (eluant; 1% acetic acid:9% methanol:90% chloroform)

Sources & evidence

ORD record: ord-691f466e543a41049449bf3410d4eae3
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202858B2

Reaction notes

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